EP2275164A1

EP2275164A1 - Multichannel micro-needles

Info

Publication number: EP2275164A1
Application number: EP09165602A
Authority: EP
Inventors: Francois Cannehan; Astrid Cachemaille
Original assignee: Debiotech SA
Current assignee: Debiotech SA
Priority date: 2009-07-15
Filing date: 2009-07-15
Publication date: 2011-01-19
Also published as: JP2012532709A; CN102625721A; RU2012102824A; BR112012000812A2; EP2453971A1; US9333330B2; US20120172820A1; JP5778144B2; WO2011006699A1

Abstract

The micro-needle (4) comprises a needle body with delivery means, a tip portion closing said delivery means and at least an opening (7,8) allowing a communication between said delivery means and the outside of the needle. Said delivery means comprise at least two inner independent lumens (5,6).

Description

TECHNICAL FIELD

The present invention concerns micro-needles that can be used for the delivery of drugs, for example for a transdermal and/or intradermal fluidic delivery of such drugs.
More specifically, the present invention concerns such micro-needles that have more than one channel or lumen that can be used for the delivery and/or removal of fluids.

BACKGROUND ART

In the frame of biomedical applications, it has become important to deliver small quantities of liquids through the stratum corneum of humans into the underlying tissue or also to sample fluids from the underlying tissue. For this purpose, micro-needles have been developed in the prior art. Due to their small dimensions, such micro-needles can be inserted into the skin without pain and cause less tissue damage than conventional hypodermic needles. In the field of transdermal and/or intradermal application such micro-needles have the potential to become the preferred drug delivery device.
Micro-needles are usually split in two main categories: solid or hollow micro-needles. Solid micro-needles do not in principle allow an active administration of a substance such as a drug but rather use a coating of the needle to deliver the substance through the skin.
In the case of hollow needles, they have a channel or lumen that is able to direct the substance through the skin. Different hollow out-of-plane micro needle for transdermal and/or intradermal applications have been described in the past. They are usually arranged in two dimensional arrays to decrease flow resistance through the device. The array can be achieved with wafer level processing. The openings are at the top of the needle, a design that increases the risk of clogging or coring. Examples of such needles are disclosed for example in the following patents: US 6,132, 755 and US 6,334, 856 , the contents of which are incorporated by reference in their entirety in the present application.
Other different designs exist for example with a traversing hole opening at the tip of the needle (see for example D.V.McAllister et al. «Microfabricated needles for transdermal delivery of macromolecules and nanoparticles : fabrication methods and transport studies », Proc. Natl. Acad. Sci. U.S.A, vol. 100, no. 24, pp. 13755-60, 2003 ) or to a side as disclosed in WO 02/17985 or in US 2004/0267205 and in WO 03/015860 , all entirely incorporated by reference in the present application.
More specifically, patent publications US 2004/0267205 and WO 03/015860 , corresponding to EP 1 416 996 (all entirely incorporated by reference in the present application) disclose micro-needles and a method for manufacturing said micro-needles. According to these publications, the micro-needle usually protrudes from a support member and comprises a micro-needle body portion, a closed pointed tip portion closing off a lumen in the tip region, and a cylindrical inner lumen extending through said support member and into said protruding needle. The needle body portion has at least one side opening communicating with said inner lumen, and the exterior envelope surface of the needle structure intersects the envelope surface of the cylindrical inner lumen within the needle structure in at least one defined region, so as to create at least one side opening in said body.
Such micro-needles and other known ones have one single inner lumen for the drug passage and one or several openings for the drug administration itself. Even if they have several openings, they still have one single supplying lumen. In case of obstruction for example by a particle or a part of the skin, a common risk considering the sizes of these needles, the needle becomes then useless. The single hole also has either a small diameter, thus a high flow resistance, or a large diameter making the needle more fragile.

SUMMARY OF THE INVENTION

It is therefore an aim of the present invention to improve the known micro-needles and to overcome the drawbacks of known devices and methods.
More specifically, an aim of the present invention is to provide improved micro-needles of the type disclosed in US 2004/0267205 and WO 03/015860 .
Another aim of the present invention is to provide micro-needles that have a better functioning and present less risk of being blocked by particles or skin parts.
Another aim of the present invention is to provide micro-needles that have a multiple channels or lumens (both words being used indifferently in the following description) offering an overall smaller flow resistance, while being more resistant to breakage.
An idea of the present invention is accordingly to form several delivery lumens in the needle instead of a single lumen thus diminishing the risk of obstruction. In addition, if one lumen is closed or blocked, there is still at least another lumen that can be used for the delivery of drug or other products.
Another advantage of the present invention is to be able to deliver different drugs with the same device during the same injection or sequentially through the different channels.
A further advantage is that the same micro-needle can be used for the delivery of drug in one channel (or several channels) and simultaneously for the removal of another liquid by another channel (or by several channels). An example of use being the sampling of interstitial fluid for glucose measuring, while administering insulin in another channel. Another example of use in the field of diagnostics is the sampling of interstitial fluid in several independent channels with a separate measurement in each one of the channels and comparison of the value measured or sequential measurement in each channel at different time intervals.
A further advantage is the opportunity to create variable size of channels, depending on the flow resistance needed. In the event of variable delivery rates needed for different drugs, a same fluid pressure would result in variable delivery rates depending on each channel used. The same would apply in the event where fluid delivery and sampling would require different flow resistance according to the injection site. An example would be that a large channel would be used for the sampling, given the low interstitial fluid pressure, and a small channel for the drug delivery given a controlled higher pressure or required lower flow rate for the drug to be delivered.
As mentioned, depending on the number of channels in the needle, each channel or combination of channels may have a dedicated use (injection and/or removal).
In principle, the methods used to form such needles do not change so the examples given in the prior art, typically as in US 2004/0267205 or WO 03/015860 are applicable to the micro-needles according to the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 illustrates an example of a needle of the prior art according to US 2004/0267205 or WO 03/015860 ;
Figures 2 illustrates in cut view an embodiment of the present invention;
Figures 3 and 4 illustrate perspective views of a set of needles according to the invention;
Figures 5 to 7 illustrate different configurations of multichannels micro-needles in cut view;
Figures 8 and 9 are SEM images of micro-needles according to the present invention;
Figures 10 and 11 illustrate possible embodiments of reservoirs for the microneedles.

DETAILED DESCRIPTION

The invention will be better understood from the following description of embodiments thereof and of the accompanying figures.
In figure 1, as mentioned above, an example of a micro-needle 1 according to the prior art (such as in US 2004/0267205 ) is illustrated. This micro-needle comprises one single delivery channel 2 and several side openings 3 for the delivery of drug. For further description of this prior art design, reference is made to the cited patent publications that are incorporated by reference in the present application for this purpose.
Figure 2 illustrates in axial cut view an embodiment of a micro-needle 4 according to the principle of the present invention. The micro-needle 4 contains at least two independent channels 5, 6 each ending at the tip of the needle 4 in an opening 7 and 8.
Figure 3 and 4 illustrate perspective views of a set of nine micro-needles 9 made according to the principle of the present invention. These micro-needles have each four channels, according to the principle of the present invention ending in four corresponding openings 10 near the tip of the needle.
Figures 5 to 7 illustrate schematically different possible configurations of lumens in cut views.
More specifically, figure 5 shows a configuration with two lumens 11, figure 6 a configuration with three lumens 12 and figure 7 a configuration with six lumens 13.
Figures 8 and 9 are SEM (scanning electron microscope) images of an array of micro-needles (figure 8) or a single micro-needle (figure 9) according to the present invention. This is an example where each micro-needle has three lumens.
In figures 10 and 11, one has illustrated possible embodiments of reservoirs for the microneedles. In the prior art, such reservoirs were typically made in a separate and/or independent part and then connected to the microneedles.
In the present invention, it is proposed to form the reservoirs directly in or partially in the support of the microneedles as illustrated in figures 10 and 11. More specifically, in figure 10 one sees in a partial cut view a microneedle 14 with openings 15 in connection with lumens 16. The design of this needle is similar to the other needles illustrated in the previous figures. This needle 14 is formed with a base 17 (as the previous embodiments disclosed above) and said base 17 comprises a recess 18 forming a part of a reservoir. There is a further element 19 attached to the base 17. This element is made from an appropriate material, for example pyrex or any other suitable material and is attached to the base 17 for example by bonding. This element 19 also comprises a recess 20 and both recesses 18 and 20 form together the reservoir that is connected to the lumen 16. Figure 10 also illustrates an inlet 21 for the reservoir for filling said reservoir with a drug or any other product to be used.
Figure 11 illustrates a perspective view in transparency of an embodiment of a needle 22 with three reservoirs 23, 24 and 25, which is for example based on the example of figure 10. Also illustrated are three inlets 26, 27 and 28 for the reservoirs 23-25. Preferably, in this embodiment, each reservoir is connected to one lumen allowing this design to deliver up to three different products, i.e. drugs according to the principle of the present invention.
Of course, this is only an exemplary embodiment and variations are possible in the frame of the present invention.
Although the lumens are illustrated in the figures as being symmetrical in cross section, they of course can be asymmetrical and can have independent variable diameters representing different flow resistances. An example would be in the case of use of the micro-needle with a multiple drug delivery system, where different rates are required for each drug and similar pressure or diffusion characteristics are applicable to each the several drugs connected to a different channel. They also may have different shapes than that represented and different sizes and the number of lumens per needle is also not limited to the configurations illustrated here, i.e. at least two or more. Also, they may be distributed in a symmetrical or non symmetrical way around the longitudinal axis of the micro-needle. An example would be, in the case of interstitial fluid sampling and drug injection in diabetes patients, that the channels would be placed in opposite directions to limit cross interaction between insulin delivery and interstitial fluid sampling.
The shapes of the lumen in cross section can be a circle, a triangle, a polygon or any other suitable shape (see figures 5-7 for some examples).
As one will readily understand, the prior art designs with one single lumen only allowed the creation of one single injection site. With the present invention, it is possible to create a plurality of independent injection sites (one for each lumen). As said previously, this gives the possibility to inject different products, i.e. drugs (one per lumen), but also to inject a product in one lumen and to recuperate another product through another lumen (for example by aspiration), while limiting the interactions between the two fluids.
When using all the lumens for the same product (for example a drug), it is possible to obtain a better homogeneity around the micro-needle than what was previously possible with a single lumen. Also, by using more than one lumen for the same product, the overall fluidic resistance is reduced and a greater quantity of product can be injected during the same time duration thus improving the flow of the micro-needle while increasing the overall micro-needle resistance to breakage.
In addition, although in the prior art according to US 2004/0267205 or WO 03/015860 , one improvement was seen in providing openings on the side rather than top of the tip, in the present invention, both configurations can be used, meaning that one lumen could end with an opening in the top of the tip, and other lumen(s) could end in an opening on the side of the tip. Typically this configuration could be chosen when it is wished to use the lumen ending in the top of the tip to stamp out a piece of tissue or to target a specific region of the skin, different from the other lumen. This was seen as a disadvantage in the prior art but here it could be useful in certain configurations. Also, this configuration is not limited to one lumen ending at the top of the tip and another lumen ending to the side of the tip, but any combination might be envisaged in the frame of the present invention.
In an embodiment each lumen can be connected to a different reservoir when all the lumen are used to delivery a fluid or other equivalent product.
The lumens dimensions and design may be calculated in order to have different flow resistance, resulting in different flow rates.
In an embodiment, the micro-needle according ot the present invention is used for the delivery of at least two drugs from a patch reservoir.
In an embodiment, the micro-needle is used for the delivery of at least one drug inside the skin (for example insulin) and a sampling of at least one substance from the skin (for example glucose from the interstitial fluid).
A further advantage of the design according to the present invention resides in the presence of a cylinder in the needle. This cylinder is visible and referenced as 30 in the figures 2, and 5-7. As one can understand this cylinder typically present in the central area of the needle 4 (for example it extends axially) and is surrounded by the lumens/channels. The advantage of this cylinder (which is absent in the prior art), is that it reinforces the needle without changing the dimension of the needle and increases it resistance to breakage.
It is clear that all the embodiments described in the present application are nonlimiting examples and other variants are possible in the scope of the present invention.

Claims

A micro-needle (4) comprising a needle body with delivery means, a tip portion closing said delivery means (5,6) and at least an opening (7,8) allowing a communication between said delivery means and the outside of the needle, wherein said delivery means comprise at least two inner independent lumens (5,6).
A micro-needle according to claim 1, wherein it comprises three or more lumens.
A micro-needle according to claim 1 or 2, wherein the lumen are symmetrically or asymmetrically distributed around the longitudinal axis of the micro-needle.
A micro-needle according to one of the preceding claims, wherein the lumens are symmetrical or asymmetrical in cross section.
A micro-needle according to one of the preceding claims, wherein the lumen have the same size or a different size in cross section.
A micro-needle according to one of the preceding claims, wherein said openings of said delivery means are on a side of said tip.
A micro-needle according to one of the preceding claims, wherein at least one opening is a the top of the tip.
A micro-needle according to one of the previous claims, wherein at least two lumens are used for different purposes.
A micro-needle according to claim 8, wherein one lumen is used for injection while another lumen is used for sampling of liquid.
A micro-needle according to claim 8 or 9, wherein each lumen is connected to a different reservoir.
A micro-needle according to claim 10, wherein the lumens are dimensioned in order to have different flow resistance, resulting in different flow rates.
A micro-needle according to one of the previous claims, wherein it is used for the delivery of at least two drugs from a patch reservoir.
A micro-needle according to one of the previous claims, wherein it is used for the delivery of at least one drug inside the skin and a sampling of at least one substance from the skin.
A micro-needle according to claim 14, wherein the delivery is of insulin and the sampling is of glucose from the interstitial fluid.